Diabetic Nephropathy

Overview

Diabetic Nephropathy is a microvascular complication of long-term Diabetes Mellitus Type I or Type II and is one of the most common causes of chronic renal failure in the US.

Pathogenesis

Early on, patients with diabetes mellitus display an increase in their Glomerular Filtration Rate (GFR) and this is thought to play an important role in the pathogenesis of diabetic nephropathy. However, how glomerular hyper-filtration arises and how it is ultimately connected to the ensuing morphological and clinical changes of diabetic nephropathy is not well-understood. Although initially increased, the progressive glomerular sclerosis which ensues is ultimately responsible for a reductions in GFR and renal function, finally ending in overt chronic renal failure.

Morphology

Glomerular Basement Membrane

The glomerular basement membrane progressively thickens in patients with Diabetes Mellitus. Indeed, basement membrane thickening appears to be a common feature in those with DM and occurs in a wide variety of non-renal capillaries as well.

Mesangium

The glomerular mesangium can display two types of sclerosis in patients with diabetes

"Diffuse Glomerulosclerosis" refers to expansion of the acellular mesangium with some mild proliferation of mesangial cells; however this is a rather unspecific finding as it can occur in a number of other pathologies

"Nodular Glomerulosclerosis" refers to development of acellular nodules within the glomerulus, termed "Kimmelstiel-Wilson Nodules" and is effectively pathognomonic for Diabetes Nephropathy

Nodules may increase in number and expand over time, pushing against the glomerular capillaries and in some cases obliterating them. Progressive pressure against and obliteration of glomerular capillaries over time reduces downstream blood flow to the remainder of the nephron. When this occurs in enough glomeruli the renal interstitium can become highly prone to ischemic injury and can increase the risk of necrotizing papillitis.

Clinical Consequences

The first clinical sign of diabetic nephropathy is the development of microalbuminuria which may last for years prior to any further clinical progression. For many patients however, these initially low levels of urinary albumin excretion rises over time and develops into overt proteinuria with concomitant nephrotic syndrome (i.e. proteinuria, hypoalbuminemia, generalized edema, hyperlipidemia, and hypercholesterolemia). Ultimately, if other complications of diabetes mellitus do not result in death, chronic renal failure will ensue.